The epidemiology of the acquired immunodeficiency syndrome (AIDS) suggests that it is caused by a blood-borne immunosuppressive virus. There is a great need to develop rapid and specific tests for AIDS-related agents, both for the diagnosis and management of patients and for the identification of blood units at risk for the transmission of disease. For the past two years, we have conducted studies of AIDS and related problems in populations of gay males, and have developed techniques for the detection of viral nucleic acids in clinical specimens. Dr. McCutchan has maintained the San Diego County AIDS registry, directed the University-based clinic for gay men and conducted studies of immune function in these patient groups. Dr. Spector has developed cloned probes to detect cytomegalovirus (CMV) DNA in clinical specimens including buffy-coats and urine. Dr. Richman has developed assays for the detection of herpes simplex virus, influenza virus and Chlamydia trachomatis nucleic acids in clinical specimens. He has also worked on the development of more sensitive hybridization assays and the application of non-radioactive nucleic acid detection techniques suitable for clinical laboratories. We now propose to evaluate assays for the detection of viral nucleic acids (initially CMV, Epstein-Barr virus and human T-cell leukemia virus) and for two promising immunologic indicators of early immunologic disturbances (Beta 2-microglobulin and lymphocyte 5 feet nucleotidase) in several well-characterized study groups. The specimens collected for both cross-sectional and longitudinal studies of different risk groups should permit the determination of both the sensitivity and specificity of these assays for detecting individuals (and their blood units) at high risk for AIDS agents. These well-characterized specimens will also be valuable for the study of nucleic acid detection assays for new candidate agents as they are proposed. These assays will be adapted and evaluated for large screening in the clinical laboratory setting.